Interface Tissue Fibroblasts from Loose Total Hip Replacement Prosthesis Produce Receptor Activator of Nuclear Factor-kB Ligand, Osteoprotegerin, and Cathepsin K

JAMI MANDELIN, TIAN-FANG LI, MIKA HUKKANEN, MIKKO LILJESTRÖM, JARI SALO, SEPPO SANTAVIRTA, and YRJÖ T. KONTTINEN

ABSTRACT.

Objective. The highly osteolytic interface tissue between the bone and loosening total hip prosthesis is characterized by low pH, formation of foreign body giant cells, osteoclasts, and production of receptor activator of nuclear factor-kB (RANKL) and cathepsin K. We hypothesized that fibroblasts in the interface tissue may form a source for RANKL production.

Methods. Primary interface tissue fibroblasts, fibrous joint capsule fibroblasts, and trabecular bone osteoblasts were stimulated with tumor necrosis factor-a (TNF-a), interleukin 1ß (IL-1ß), IL-6, IL-11, or 1a,25-(OH)₂ vitamin D₃. Cellular RANKL and released cathepsin K were detected by Western blotting. RANKL in cell lysates and osteoprotegerin (OPG) in cell culture medium were measured by ELISA. RANKL, OPG, and cathepsin K mRNA were measured with quantitative reverse transcriptase polymerase chain reaction.

Results. Interface tissue fibroblasts were found to produce RANKL. 1a,25-(OH)₂ vitamin D₃ stimulation increased RANKL mRNA expression. TNF-a was found to be the most potent OPG inducer in interface tissue fibroblasts. Cathepsin K mRNA production in fibroblasts was upregulated roughly 3-fold (p < 0.01) after 1a,25-(OH)₂D₃ stimulation, and both pro- and active cathepsin K protein was released to fibroblast culture media.

Conclusion. Interface tissue fibroblasts are able to produce RANKL, OPG, and cathepsin K and may contribute indirectly and directly to pathologic periprosthetic collagenolysis and bone destruction. (J Rheumatol 2005;32:713-20)

Key Indexing Terms:

CATHEPSIN K
FIBROBLAST
IMPLANTS
OSTEOPROTEGERIN
RANKL
VITAMIN D

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From the Institute of Biomedicine/Anatomy, Biomedicum Helsinki, University of Helsinki; Department of Orthopaedics and Traumatology; Department of Medicine/Invärtes Medicin, Helsinki University Central Hospital; ORTON Orthopaedic Hospital of the Invalid Foundation, Helsinki; and COXA Hospital for Joint Replacement, Tampere, Finland.

Supported by the Academy of Finland, TEKES, Sigrid Jusélius Foundation, the Invalid Foundation, Helsinki University Hospital (TYH 0341, TYH 1233, TYH 2267), and Biomedicum Helsinki research funds. J. Mandelin was supported by the University of Helsinki Science Foundation and Emil Aaltonen Foundation (Young Investigator grants).

J. Mandelin, MSc; T-F. Li, MD, PhD; M. Hukkanen, PhD; M. Liljeström, MSc, Institute of Biomedicine/Anatomy, Biomedicum Helsinki, University of Helsinki; J. Salo, MD, PhD; S. Santavirta, MD, PhD, Department of Orthopaedics and Traumatology, Helsinki University Central Hospital; Y.T. Konttinen, MD, PhD, Department of Medicine/Invärtes Medicin, Helsinki University Central Hospital, ORTON Orthopaedic Hospital of the Invalid Foundation, Helsinki, and COXA Hospital for Joint Replacement, Tampere, Finland.

Address reprint requests to Dr. Y. Konttinen, Biomedicum Helsinki, Helsinki University Central Hospital, PO Box 700, Helsinki, FIN-00029, Finland. E-mail: yrjo.konttinen@helsinki.fi

Accepted for publication December 31, 2004.

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